Loading...
dcyphr | Postnatal HIV transmission in breastfed infants of HIV-infected women on ART: A systematic review and meta-analysis

Abstract

In this literature review, the researchers wanted to understand the risk of mother-to-child transmission of HIV through breastfeeding if the mother received antiretroviral therapy (ART). The researchers reviewed experimental and observational studies. Exposure was maternal HIV antiretroviral therapy and different ways of infant feeding (breastfeeding, bottle-feeding, etc.). Outcomes were defined as overall and postnatal HIV transmission rates at 6, 9, 12, and 18 months. Literature from 2005-2015 was searched in multiple databases. Papers were analyzed by narrative synthesis, meaning the review relied on the use of words and text to organize data. The data was pooled using a statistical method called random effects meta analysis. HIV transmission after birth was assessed from four to six weeks of life. The quality of the study was assessed using a modified Newcastle-Ottawa Scale (NOS) and GRADE. 11 studies were identified for the study. Overall, pooled transmission rates at 6 months for breastfed infants whose mothers were undergoing ART was 3.54% and 4.23% at 12 months. Postnatal transmission rates were 1.08 at 6 months and 2.93 at 12 months. ART was provided for prevention of mother-to-child transmission (PMTCT) and was discontinued after 6 months in these studies. In conclusion, there is evidence that maternal ART significantly decreases the risk of postnatal HIV transmission. However, transmission risk increased after ART for PMTCT was discontinued after 6 months, which supports the WHO recommendations of life-long ART for all.

Aims

The researchers wanted to review literature about mother-to-child transmission of HIV in breastfed infants whose mothers received antiretroviral therapy. They did this to support the process of updated the World Health Organization infant feeding guidelines in the context of HIV and ART.

Introduction

There has been significant progress in decreasing the number of new HIV infections in children. This progress is consistent with increased coverage and quality of antiretroviral treatment (ART) programs that provide prevention of mother-to-child transmission. HIV transmission from mother to child can occur during pregnancy, delivery, and breastfeeding. However, breastfeeding has substantial benefit for infant health and survival, so minimizing the risk of transmission during breastfeeding is important. The World Health Organization (WHO) recommends that breastfeeding, HIV-positive mothers should breastfeed infants under the cover of maternal or infant ART.

In most African countries and some parts of India, health policy continues to advise mothers with HIV to breastfeed under the cover of maternal or infant ART. However, these recommendations are supported by limited information on the risk of postnatal HIV transmission when the infant, mother, or both are on ART to prevent mother-to-child transmission (PMTCT). In addition, there was little information on whether mixed feeding (breastfeeding and formula), which had been associated with increased risk of postnatal transmission, remained a risk in the presence of ART.

In recent years, evidence has shown that PMTCT was achieved postnatally through maternal ART or infant prophylaxis. The risk of transmission when infants receive mixed feeding is of significant interest to public health. In this study, the researchers address the question of HIV transmission at 6, 9, 12, and 18 months in infants born to women who were on ART from early-mid pregnancy until 6 months after birth, and whose infants breastfed in the first 6 months of life.

Methods

This literature review considered experimental and observational studies. It included HIV-positive mothers receiving ART and their breastfed children regardless of if the infant was receiving antiretroviral prophylaxis. The variables of the review were HIV antiretroviral therapy and feeding method during breast-feeding (exclusively breastfeeding, mixed breastfeeding/replacement feeding, exclusively replacement feeding). Outcome measures were overall and postnatal HIV transmission rate at 6, 9, 12, and 18 months.

The researchers searched multiple databases for articles publishes between 2005 and 2015. Studies were first selected for eligibility based on their abstracts. Then, the full texts were assessed. Data was extracted from these studies. Figure 1 shows a flowchart of the screening process for these studies.

To obtain more information about infant feeding, the first authors of 7 studies were contacted and questioned. 3 responded. Questions related to the type and duration of recommended feeding practice, type of infant feeding support given to mothers, collection of data on child feeding practices, and how this data was addressed in the study.

The studies included in the review were assessed using a modified Newcastle-Ottawa Scale (NOS), which the authors developed. The NOS assessed the quality of studies included based on the selection of study participants and outcome assessment.

The results of the review were analyzed using STATA. The researchers used random effects meta-analysis because of methodological differences between studies, so they could ascertain true transmission rates.

Results

11 studies were selected for inclusion in the review. 4 were randomized clinical trials and 7 were observational studies. In all studies, mothers started ART before or during pregnancy and continued through 6 months after birth.

HIV transmission

Of 11 studies, 8 reported transmission rate at 6 months. 2 studies did not provide a confidence interval around the estimated transmission rates, so the researchers calculated it themselves. 2 studies reported the number of infections at 6 months and the number of children at risk, so the researchers also calculated transmission rate for these studies. 2 more studies reported number of transmissions but not number of children at risk. 1 study reported transmission only at 9 months but noted that all transmissions occurred during breastfeeding.

Overall transmission at age six months

6 studies provided overall transmission rates at 6 months. In 2 studies, ART was provided since 15 weeks of pregnancy. Of these studies, one reported an overall transmission rate of 1.4%, while another reported a transmission rate of 1.9%.  Another study did not describe time for beginning ART, and the reported transmission rate was 0.5%.

Subsequent studies started ART at later stages, from 30-34 weeks of pregnancy. Studies reported transmission rates of 7.9%, 5.0%, 5.0%, and 3.4-7.4%.

The pooled estimate of overall transmission at 6 months was 3.54%.

Postnatal transmission between four and six weeks and six months

6 studies provided estimates of postnatal transmission rates. 3 studies provided ART since the first physician visit after birth. One study reported a transmission rate of 0.2%, while another reported a rate of 0.6% after 4 weeks of age. Another study reported a rate of 3.1%, noting that one of the infants was mixed fed.

In the other 3 studies, transmission rates were reported to be 2.7%,  0.80%, and 0.3-2.4%. The pooled transmission rate in these studies was 1.08%.

Rate of transmission assessed after 6 months of age

Of 7 studies providing information on transmission rates at 12 months, 5 reported overall HIV transmission rates and 2 reported postnatal transmission rates. Pooled estimates showed a 4.2% transmission rate at 12 months, and a postnatal transmission rate of 2.93%.

One study reported overall and postnatal transmission at 9 months of age, at 1.8% and 0.5% respectively. Another estimated overall and postnatal transmission at 5.3% and 1.2% respectively.

Four studies reported a rate of transmission at 18 months, but could not be pooled due to large differences between them. Only one study reported an estimated overall rate of transmission, at 4.1%. Two other studies provided overall transmission at 18 months, at 6.0% and 6.7%. In both studies, mothers started ART at 34 weeks pregnant and stopped at 6 months after birth.

Discussion

This review is the first synthesis of HIV transmission risk in infants with HIV-positive mothers, including mothers receiving lifelong ART. The review provides evidence that postnatal HIV transmission risk is low in the presence of maternal ART. The researchers found a pooled estimated overall transmission rate of 3.5% and postnatal transmission rate of 1.1% in women who were on ART from early-mid pregnancy and who were recommended to breastfeed their children for 6 months. The pooled estimate for postnatal transmission at 12 months of age was 3.0%. Only one study provided an estimation of transmission rate at 18 months at 4.1%.

The results of this review show decreased rates of transmission from the pre-ART era, which ranged from 15% at six weeks and 32% at six months. This decrease highlights the efficacy of ART and the importance of early initiation and adherence to ART in pregnancy.

Exclusively breastfeeding for the first 6 months of life is recommended for its positive effect on reducing infant and child mortality and long-term health outcomes. Before WHO guidelines recommending ART to reduce postnatal transmission, refraining from mixed-feeding in the first 6 months was considered important due to the risk of postnatal transmission. The rate of transmission associated with mixed feeding could not be estimated.

In the included studies, women were recommended to exclusively breastfeed for 6 months according to WHO guidelines, but there was no specific support for mothers to exclusively breastfeed. Because of this, findings from this review reflect real-world situations. However, two reports included in the review suggest that support may increase adherence to breastfeeding.

The WHO also recommends introducing complementary foods in addition to breastfeeding after six months. However, it also recommends that HIV-positive women are recommended to breastfeed for one year while receiving ART. Only two studies followed the latter recommendation. In other studies, there was continued transmission after six months due to continued breastfeeding without ART cover. 

This review highlighted clinical and methodological differences in time of ART initiation during pregnancy, recommended duration of breastfeeding, and the age at which infection in infants was assessed. The researchers also calculated transmission rates, which were not provided by all studies, which contributes to the low quality of evidence concerning risk associated with continued breastfeeding between 6 and 12 months. This review informs understanding of transmission in the postnatal period in women who receive ART. The findings of this review demonstrate a lower risk of postnatal transmission when women are on ART and breastfeeding. The quality of the evidence is low. New WHO guidelines on initiation of ART for all HIV-positive people upon diagnosis will expand ART coverage in breastfeeding women.